This proposal details a comprehensive 5-year training program for my career development in cardiovascular research. This plan is designed to provide the additional scientific and technical training that will prepare me for an independent career in academic research. With the support provided by this grant, I will seek additional formal training in ion channel biophysics and the mathematical sciences and further my technical expertise with patch clamp techniques and in vitro analysis of cellular electrophysiology. Sudden cardiac death claims the lives of 350,000 Americans each year (equivalent to 1000 people a day or one person every two minutes). Many of these events occur as a consequence of inherited arrhythmias that cause dysfunction of ion channels, or channelopathies. The central hypothesis of this proposal is that the cardiac specialized conduction system, comprised of Purkinje fiber (PF) cells, plays a central role in the formation and maintenance of these deadly arrhythmias. In this proposal, the Purkinje system will be studied in a combined in vitro and computational approach in order to examine a novel paradigm: whether differences in tissue type and their interplay modulate the cellular effect of heritable channelopathies. The findings promise to have important implications in the pharmacologic management of affected patients. The insight gained may also enhance our understanding of channel dysfunction in more widespread cardiovascular conditions, such as heart failure and ischemia. My aims are: 1. To investigate how changes in cell type regulate channel dysfunction in single/isolated Purkinje fiber (PF) cells and ventricular myocyte (VM) cells. 2. To study the cellular triggers of arrhythmi in channelopathy using an experimental mouse model, alongside the corresponding computational model. 3. To utilize multidimensional simulation to determine the impact of mutations in the Purkinje fiber system and interplay with the ventricle, establishing a link between genetic lesion and arrhythmia on the whole organ level.